Plasminogen plasma concentration

Plasminogen activator inhibitor type 2 (PAI-2) is present in human placenta and monocytes (37, 42). The single-chain inhibitor molecule (sPAI-2) inhibits both two-chain u-PA and two-chain t-PA. Its inhibition is 10 times greater for two-chain u-PA compared with two-chain t-PA and it inhibits single-chain t-PA only minimally (37). Plasma concentrations of PAI-2 up to 2 p,M have been observed in the third trimester of pregnancy (42). 

Additionally, attention has been focused on some factors that, operating in the hemostatic balance, have been attributed the role of risk markers of clinical events. Thus, increased plasma concentration of factor VII, fibrinogen, plasminogen activator inhibitor type 1 (PAI-1), and the already mentioned Lp(a) have been associated with the occurrence of CHD. Much work has been done on the modulation of these factors by HT (for a review see Cano and Van Baal 2001), and both similarities and differences have been found in the sparse literature on SERM action. Raloxifene and droloxifene decrease fibrinogen more actively than does HT (Walsh et al. 1998 Herrington et al. 2000). In contrast, the effective reduction demonstrated for PAI-1 with oral HT was not confirmed for raloxifene or droloxifene (Walsh et al. 1998 de Valk-de Roo et al. 1999 Herrington et al. 2000). 

The effect of continuously administered low-dose 17-beta-estradiol (E2) + norethisterone acetate (NETA) on coagulation and fibrinolytic factors has been studied in 120 menopausal women, using two dosage variations (1 mg of E2 with 0.25 mg or 0.5 mg of NETA) compared with placebo over a year (53). In either dose, the combination significantly lowered plasma concentrations of factor VII, fibrinogen, antithrombin, and plasminogen activator inhibitor-1 (PAI-1) compared with placebo. These changes appear favorable, since they may lead to increased fibrinolytic activity and could reduce the risk of coronary heart disease. However, antithrombin activity was also reduced, which may increase the risk of venous thromboembolism. 

Ostrowski SR, Ullum H, Goka BQ, Hoyer-Hansen G, Obeng-Adjei G, Pedersen BK, et al. Plasma concentrations of soluble urokinase-type plasminogen activator receptor are increased in patients with malaria and are associated with a poor clinical or a fatal outcome. J Infect Dis 2005 191(8) 1331-1341. 

Plasminogen is the precursor of the serine protease plasmin which is involved in dissolution of fibrin clots and, hence, in removal of thrombi. The plasma concentration is about 12mg/100ml and the molecular mass 81 kDa. It contains 17.1% carbohydrate on two sites, one N-linked and one O-linked oligosaccharide. A variant is also known that is only 0-glycosylated. The structures of the oligosaccharides have been determined [71-73], and are shown in Fig. 11. 

M Ranby, N Bergsdorf, T Nilsson, G Mellbring, B Winblad, G Bucht. Age dependence of tissue plasminogen activator concentrations in plasma, as studied by an improved enzyme-linked immunosorbent assay. Clin Chem 32 2160,... 

B5. Borgfeldt, C., Bendahl, P. O., Ferno, M., and Casslen, B., High preoperative plasma concentration of tissue plasminogen activator (tPA) is an independent marker for shorter overall survival in patients with ovarian cancer. Gynecol. Oncol. 91, 112-117 (2003). 

K7. Kruithof, E. K. O., Nicolosia, G., and Bachman, F., Plasminogen activator inhibitor 1 Development of a radioimmunoassay and observations on its plasma concentration during venous occlusion and after platelet aggregation. Blood 70, 1645-1651 (1987). 

Tincture of the dried seed, on agar plate at a concentration of 30 p,L/disc, was inactive on Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. Extract of 10 g plant material in 100 mL ethanol was used b Anticoagulation activity. Serpin BSZx (an inhibitor of trypsin and chemotrypsin) inhibited thrombin, plasma kallikrein, factor Vlla/tissue factor, and factor Xa at heparin-independent association rates. Only factor Xa turned a significant fraction of BSZx over as substrate. Activated protein C and leukocyte elastase were slowly inhibited by BSZx, whereas factor Xlla, urokinase and tissue type plasminogen activator, plasmin and pancreas kallikrein, and elastase were not or only weakly affected. Trypsin from Fusarium was not inhibited, while interaction with subtilisin Carlsberg and Novo was rapid, but most BSZx was cleaved as a substrate L... 

Plasminogen is inherited as two codominant autosomal alleles. Fetal synthesis and the absence of transplacental passage have been demonstrated. In newborns there is a decrease in both plasma plasminogen concentration, and functional plasminogen activity, suggestive of a fetal dysfunctional plasminogen molecule. Several hereditary dysfunctional molecules have been described in adults with recurrent thromboembolic disease. The defects in these molecules include abnormal active sites, impaired activator binding, and defective activation. 

Slot O, Brunner N, Locht H, Oxholm P, Stephens RW. Soluble urokinase plasminogen activator receptor in plasma of patients with inflammatory rheumatic disorders Increased concentrations in rheumatoid arthritis. Ann Rheum Dis 1999 58(8) 488-492. 

Unfavorable reactions can occur when transiently high concentrations of a drug or its vehicle are attained rapidly in plasma and tissues. There are therapeutic circumstances where it is advisable to administer a drug by bolus injection (e.g., tissue plasminogen activator) and other circumstances where slower administration of drug is advisable (e.g., antibiotics). 

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